The use of interspecific hamster-mouse somatic cell hybrids has greatly expanded our studies on the genetic control of the transmission and expression of murine leukemia viruses. Hybrids are being used to identify and chromosomally map specific genes involved in viral leukemogenesis, and to simplify their further analysis by constructing cell lines carrying isolated genetic elements from this complex multigene system. Recent studies have demonstrated that the ecotropic and recombinant MCF viruses require different cell-surface receptors to infect mouse cells; genes for these receptors have been mapped to different chromosomes. Receptor loci for mouse leukemia viruses are also being identified and mapped in other species using cat-hamster and human-hamster hybrids. Hybrids which lack receptors are being used to describe the patterns of expression characteristic of specific engdogeneous V loci. Finally somatic cell hybrids are being analyzed with molecularly cloned viral probes to describe the chromosomal location and organization of these proviral sequences.